Each year, hundreds of thousands of jaundiced newborns receive phototherapy to keep their bilirubin from rising to dangerous levels. However, there is little evidence to quantify either the late adverse impact of these high bilirubin levels r of the phototherapy used to prevent them. The Late adverse Impact of Getting Hyperbilirubinemia or photoTherapy (LIGHT) study will fill two key knowledge gaps that prevent evidence- based treatment of jaundice in newborns: 1) it is not known to what extent high bilirubin levels increase the risks of cerebral palsy and hearing loss, the two main adverse effects of hyperbilirubinemia; and 2) it is not known whether phototherapy itself causes late adverse effects, including leukemia, diabetes and asthma, each of which has been linked to phototherapy in previous inconclusive studies. Because both of the exposures (high bilirubin levels and use of phototherapy), and most of the outcomes (cerebral palsy, hearing loss, leukemia, diabetes) are rare, addressing these questions convincingly requires very large sample sizes. The proposed project will continue successful 20-year collaboration between investigators at the University of California, San Francisco and the Kaiser Permanente Division of Research. We will link rich databases maintained by researchers from the Northern California Kaiser Permanente Medical Care Program with newly available electronic records from the California Department of Developmental Services, which provides services to handicapped children in California. This will create a historical cohort of ~495,000 children born 1995-2011. To quantify the excess risk of cerebral palsy and hearing loss in newborns with elevated serum bilirubin levels, we will classify children according to their bilirubin levels in relation to the American Academy of Pediatrics treatment guidelines. We will compare their risks of cerebral palsy and hearing loss, ascertained through electronic medical records and the California Department of Developmental Services database of children with developmental disabilities, with confirmatory case review by a child neurologist or audiologist. To determine whether phototherapy is associated with increased risk of late adverse effects, we will classify children according to whether or not they received inpatient phototherapy as newborns. We will compare their risks of leukemia, diabetes, asthma, and other diseases using diagnoses from hospitalizations and outpatient visits, the Kaiser Permanente Northern California Cancer and Diabetes Registries and coded causes of out-of- hospital deaths, controlling for confounding using propensity scores and other multivariable analyses. The expected outcomes of this research are estimates of the adverse impact of both hyperbilirubinemia and phototherapy, which will enable more evidence-based treatment of newborns for jaundice. This could improve the health of children by reducing over- or under-treatment of neonatal jaundice with phototherapy. PUBLIC HEALTH RELEVANCE: Most newborns develop jaundice (a yellow color of the skin and whites of the eyes), but it currently is not clear which newborns should be treated with phototherapy. The proposed research is relevant to public health because it will provide information about the potential benefits and risks of phototherapy. The questions we seek to answer are relevant to the Agency for Healthcare Research and Quality's mission to improve the quality, safety, efficiency and effectiveness of health care because overtreatment of jaundice with phototherapy is inefficient, undertreatment is ineffective, and both may be unsafe.